Catheter-Directed Thrombolysis Versus Anticoagulation Monotherapy in Intermediate-High Risk PE

NCT05172115 | Terminated Phase 3 DMC

• 1 other identifier: 97056
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 1

Brief Summary

In an open-label parallel groups blinded-endpoint randomized clinical trial, the investigators aim to assess the safety and efficacy of conventional catheter-directed thrombolysis (CDT) vs anticoagulation monotherapy on outcomes of patients with acute intermediate-high risk pulmonary embolism. The investigators hypothesize that CDT will have a superior efficacy and safety compared with anticoagulation-only therapy regarding the proportion of patients with a right ventricle to left ventricle (RV/LV) ratio \> 0.9 at a 3-month follow-up by an imaging core laboratory, major bleeding, severe thrombocytopenia, or vascular access complication.

Conditions

Pulmonary Embolism; Pulmonary Thromboembolisms; Embolism, Pulmonary; Right Ventricular Dysfunction

Keywords

Intermediate-high risk pulmonary embolism; Catheter-directed thrombolysis; Anticoagulation

Outcome Measures

Primary Outcomes (1)

• The proportion of patients with a RV/LV ratio >0.9

  Proportion of patients with a RV/LV ratio \>0.9 at a assessed by an imaging core laboratory 3-month follow-up

  At 3 months from randomization

Secondary Outcomes (6)

• The proportion of patients with an RV/LV ratio >0.9

  At 72 hours from randomization

• The proportion of patients with Unrecovered RV

  At 3 months from randomization

• All-cause mortality

  Within 3-month Study period

• Major bleeding

  Within 3-month Study period

• Severe thrombocytopenia

  Within 3-month Study period

Other Outcomes (4)

• A composite of all-cause death or the primary outcome

  Within 3-month Study period

• PE-related mortality.

  Within 3-month Study period

• Hospital length of stay

  Within 3-month Study period

Study Arms (2)

Conventional catheter-directed thrombolysis (CDT)

EXPERIMENTAL

Conventional catheter-directed thrombolysis (CDT) will be the interventional arm. CDT will be administered using fixed-dose of 24 mg tissue plasminogen activator infusion over 24 hours (0.5 mg/h per catheter if bilateral or 1 mg/h per unilateral catheter) with 500 unit per hour of infusion of unfractionated heparin during the thrombolytic therapy. The therapeutic dose of heparin will immediately be substituted the CDT after termination, and twice-daily subcutaneous enoxaparin (1mg/kg) for the first 48 hours after the thrombolytic therapy will be administered. Direct oral anticoagulation will be in ones with no clinical deterioration.

Procedure: Conventional catheter-directed thrombolysis (CDT) with recombinant tissue plasminogen activator (rtPA)

Anticoagulation-only therapy

ACTIVE COMPARATOR

The anticoagulation-only therapy will be the assigned treatment in the control arm. Control patients will receive subcutaneous enoxaparin (twice-daily, 1mg/kg) in the first 48hours of enrollment. Direct oral anticoagulation will be in ones with no clinical deterioration.

Drug: Enoxaparin

Interventions

Conventional catheter-directed thrombolysis (CDT) with recombinant tissue plasminogen activator (rtPA) PROCEDURE

Conventional catheter-directed thrombolysis with fixed-dose of 24 mg tissue plasminogen activator infusion over 24 hours

Also known as: Cragg-McNamara™ valved infusion catheters

Conventional catheter-directed thrombolysis (CDT)

Enoxaparin DRUG

Subcutaneous enoxaparin twice-daily (1mg/kg)

Also known as: low molecular weight heparin (LMWH)

Anticoagulation-only therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients ≥18 years
• Confirmed acute pulmonary emboli by computed tomography pulmonary angiography (CTPA)
• Symptom onset ≤14 day
• Elevated N-terminal-proB-type natriuretic peptide and cardiac troponin
• Right ventricle/left ventricle ratio \>0.9 in transthoracic echocardiography
• Less than 48 hours of anticoagulation therapy
• Willingness for participation in the study with signed and dated informed consent form

You may not qualify if:

• Pulmonary emboli detected by modalities other than CTPA
• Segmental PE
• High risk (massive)
• Severe renal dysfunction(creatinine clearance \[CrCl\] below 30 mL/min)
• Terminal illness Surgery within 2 weeks
• Platelet count \<50.000 /µL
• Pre and post catheter directed thrombolysis echocardiography exam not possible
• Contraindication to thrombolytic therapy
• Concomitant right heart thrombi
• Allergic reaction to study medications
• Lack or withdrawal of informed consent

Sponsors & Collaborators

• Rajaie Cardiovascular Medical and Research Center: lead

Study Sites (1)

Rajaie Cardiovascular Medical and Research Center

Tehran, 1995614331, Iran

Location

Related Publications (1)

• Sadeghipour P, Jenab Y, Moosavi J, Hosseini K, Mohebbi B, Hosseinsabet A, Chatterjee S, Pouraliakbar H, Shirani S, Shishehbor MH, Alizadehasl A, Farrashi M, Rezvani MA, Rafiee F, Jalali A, Rashedi S, Shafe O, Giri J, Monreal M, Jimenez D, Lang I, Maleki M, Goldhaber SZ, Krumholz HM, Piazza G, Bikdeli B. Catheter-Directed Thrombolysis vs Anticoagulation in Patients With Acute Intermediate-High-risk Pulmonary Embolism: The CANARY Randomized Clinical Trial. JAMA Cardiol. 2022 Dec 1;7(12):1189-1197. doi: 10.1001/jamacardio.2022.3591.

  PMID: 36260302 DERIVED

MeSH Terms

Conditions

Pulmonary Embolism; Ventricular Dysfunction, Right

Interventions

carbohydrate-deficient transferrin; Enoxaparin; Heparin, Low-Molecular-Weight

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Embolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Ventricular Dysfunction; Heart Diseases

Intervention Hierarchy (Ancestors)

Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Officials

• Parham Sadeghipour, M.D

  Rajaie Cardiovascular Medical and Research Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Allocation sequence concealment and blinded outcome adjudication
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: 1:1 open-label parallel group randomized controlled trial with concealed allocation sequence and blinded outcome adjudication

Study Record Dates

• First Submitted: December 10, 2021
• First Posted: December 29, 2021
• Study Start: December 22, 2018
• Primary Completion: February 2, 2020
• Study Completion: May 2, 2020
• Last Updated: December 29, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

IR (1)